Table 2.
Metformin Pharmacokinetics in Plasma and Urine
| Arithmetic Mean (CV%) | Geometric LSM | Geometric LSM Ratio | ||||
|---|---|---|---|---|---|---|
| Pharmacokinetic Parameter | Metformin (n = 17) | Metformin + Tucatinib (n = 17) | Metformin (n = 17) | Metformin + Tucatinib (n = 17) | Estimate | 90% CI |
| Plasma | ||||||
| AUC0‐last (µg·h/mL) | 8.4 (26.2) | 11.6 (29.9) | 8.1 | 11.1 | 1.4 | 1.2‐1.5 b |
| AUC0‐inf (µg·h/mL) | 8.6 (26.4) | 12.1 (30.5) | 8.3 | 11.6 | 1.4 | 1.3‐1.5 b |
| Cmax (µg/mL) | 1.3 (18.0) | 1.5 (27.9) | 1.3 | 1.4 | 1.1 | 1.0‐1.2 |
| Tmax (h) a | 2.5 (1.5, 4.0) | 3.0 (1.0, 4.1) | — | — | — | — |
| t½ (h) | 4.5 (11.7) | 5.6 (12.2) | — | — | — | — |
| VzF (L) | 695.4 (32.6) | 627.2 (41.5) | 664.7 | 586.8 | 0.883 | 0.763‐1.021 |
| CL/F (L/h) | 105.4 (26.7) | 77.4 (34.9) | 102.0 | 73.4 | 0.72 | 0.649‐0.799 b |
| Urine | ||||||
| Ae0‐24 (mg) | 242.6 (26.5) | 190.8 (31.7) | — | — | — | — |
| Fe0‐24 (%) | 28.5 (26.5) | 22.4 (31.7) | — | — | — | — |
| CLrenal (L/h) | 30.0 (27.0) | 17.6 (36.0) | 28.79 | 16.45 | 0.571 | 0.516‐0.632 b |
Ae0–24, amount of metformin excreted unchanged in urine; AUC0‐inf, area under the plasma concentration–time curve from time 0 to infinity; AUC0‐last, area under the plasma concentration‐time curve from time 0 to the last available measurement; CI, confidence interval; CL/F, apparent oral clearance; CLrenal, renal clearance; Cmax, maximum observed plasma concentration; CV, coefficient of variation; Fe0‐24, mean cumulative fraction of metformin excreted unchanged in urine; LSM, least‐squares mean; t½, terminal elimination half‐life; tmax, time to Cmax; VzF, apparent volume of distribution.
a
Median (range) is presented.
b
Statistically significant.